"As the list of expressed human genes expands, a major scientific and medical challenge is to understand the molecular events that drive normal tissue morphogenesis and the progression of pathologic lesions in actual tissue. With the advent of polymerase chain reaction (PCR), and the development of high-throughput, automated microhybridization arrays and mutation screening methods, DNA or RNA can be extracted from tissue biopsies and analyzed with a parallel panel of hundreds or even thousands of genetic markers. Since cells in complex tissue are biochemically and physically affected by surrounding cells and by remote stimuli from greater distances, the task of analyzing critical gene expression patterns in development, normal function, and disease progression depends on the extraction of specific cells from their complex tissue milieu. Laser capture microdissection (LCM) (1) has been developed to provide a rapid, reliable method to procure pure populations of specified cells from specific microscopic regions of tissue sections for subsequent analysis. LCM offers a number of advantages. In one step, the cells of interest are transferred to the polymer film. The separate fragmentation step in conventional microdissection and the resulting contaminating debris are avoided. Secondly, only the targeted cells are affected with a precision of transfer which can approach 1 |m. Thus, the remaining tissue on the slide remains fully accessible for further capture so that comparative molecular analysis can be performed on adjacent cells. No micromanipulation is required to perform LCM. The exact morphology of the procured cells is retained and held on the transfer film, thus transfer images constitute a diagnostic record of the cells undergoing molecular analysis. LCM was conceived and first developed as a research tool at NIH and through a Collaborative Research and Development Agreement (CRADA) partnership with Arcturus Engineering, Inc (Mountain View, CA), made into a commercial instrument. LCM is being used in the Cancer Genome Anatomy Program (CGAP) effort to catalog the genes which are expressed in human tissue as normal cells undergo premalignant changes and further develop into invasive and metastatic cancer. Microarray hybridization panels containing these index sets are being used to obtain a molecular fingerprint of gene expression in microdissected human tissue biopsies. The fluctuation of expressed genes or alterations in the cellular DNA which correlate with a particular disease stage can be compared within or between individual patients. Such a fingerprint of gene expression patterns may provide crucial clues for etiology, and may ultimately contribute to diagnostic decisions and therapies tailored to the individual patient. Molecules found to be associated with a defined pathological lesion may serve as future imaging or therapeutic targets.LCM-based molecular analysis of histopathological lesions can be applied to any disease process which is accessible through tissue sampling"